1. Field of the Invention
This invention relates to tumor inhibiting pharmaceutical compositions, methods of inhibiting the growth of mammalian tumors, and 3-phenyl-5,6-dihydrobenz[c]acridine-6-carboxylic acids and derivatives thereof useful in such compositions and methods.
2. Prior Art
5,6-dihydrobenz[c]acridine-7-carboxylic acids are well-known in the chemical literature. They are generally synthesized by the Pfitzinger reaction of an appropriate isatin with an appropriate 3,4-dihydro-1(2H)-naphthalenone.
Buu-Hoi et al. [Bull. Soc. Chim. 11, 127-136 (1944); Chem. Abstr. 40:2816] report the synthesis of 7-cyclohexyl-3,4-dihydro-1(2H)-naphthalenone and its reaction with isatin.
U.S. Pat. No. 2,579,420, issued to Coles on Dec. 18, 1951, describes the conversion of 6,8-dihalocinchonic acids into 6-halo-8-hydroxy cinchonic acids useful as color formers. The patent also discloses the Pfitzinger reaction of 3,4-dihydro-1(2H)-naphthalenone with substituted or unsubstituted 5,7-dihaloisatinic acids.
Cromwell et al. [J. Org. Chem. 23, 789-793 (1958) and J. Org. Chem. 24, 1077-1080 (1959)] report the synthesis of 5,6-dihydrobenz[c]acridine-7-carboxylic acids as intermediates in the synthesis of potential carcinogenic and/or antitumor benz[c]acridines.
Braunholtz et al. [J. Chem. Soc. 3368-3377 (1958)] report the synthesis of 5,6-dihydrobenz[c]-acridine-7-carboxylic acid.
Buu-Hoi et al. [J. Chem. Soc. 2274-2279 (1963) and J. Chem. Soc. 5622-5626 (1964)] report the synthesis of benz[c]acridines as potential carcinogens.
Sy et al. [Bull. Chim. Soc. Fr. 5, 1308-1315 (1965)] report the synthesis of 5,6-dihydrobenz[c]-acridine-7-carboxylic acids.
Al-Tai et al. [J. Chem. U.A.R. 10, 339-352 (1967)] report the Pfitzinger reaction of 3,4-dihydro-1(2H)-naphthalenones.
Cagniant et al. [Bull. Soc. Chim. Fr. 3, 985-991 (1969)] report the synthesis of 5,6-dihydro-4,9-dimethylbenz[c]acridine-7-carboxylic acid.
Rosowsky et al. [J. Heterocycl. Chem. 8, 809-820 (1971)] report 7-benz[c]acridinemethanols as tetracyclic analogs of the 2-phenyl-4-quinolinemethanol antimalarials.
Cromwell et al. [J. Heterocycl. Chem. 16, 699-704 (1979)] report the synthesis of 7-substituted-5,6-dimethylbenz[c]acridines as potential carcinogenic, carcinostatic, or antiparasitic agents.
U.S. Pat. No. 4,680,299, issued to Hesson on Jul. 14, 1987, discloses tumor-inhibiting 2-phenyl-4-quinolinecarboxylic acids.
There are no literature references disclosing the 3-phenyl-5,6-dihydrobenz[c]acridine-7-carboxylic acids or derivatives thereof of this invention, or their use in inhibiting the growth of mammalian tumors.